The overall goal of this proposed research is to design, develop and translate into clinical practice a new compact terahertz (THz) imaging device for accurately assessing positive breast cancer margins during surgical breast conservation procedures (i.e., lumpectomy). In breast conservation surgery (BCS), the surgeon attempts to remove malignant tissue with a surrounding margin of healthy tissue. After the surgical excision of the tumor, the specimen is submitted to pathology for evaluation to determine if the margins are clear of malignant tissue. Pathological analysis typically requires at least one day before results can be ascertained. Surprisingly, pathologic analysis currently indicates positive tumor margins about 40-50% of the time [Dillon 2007;Fleming 2004;Jacobs 2008;Waljee 2008], thereby requiring that the patient undergo a surgical re- excision procedure to remove additional breast tissue. We explain in this proposal how the proposed real-time terahertz imaging method can potentially provide accurate performance in assessing margins intra-operatively, thus eliminating many of the disadvantages with the currently used procedures, and ultimately decreasing healthcare costs. While preliminary reports have suggested that images produced with THz radiation applied to breast specimens can accurately differentiate between breast carcinoma and normal fibroglandular and adipose tissue (with much greater specificity than x-ray imaging), the challenge undertaken in the proposed effort is to further study the performance of using THz imaging to intra-operatively assess tumor margins, as well as to develop a technology (using frequency domain techniques) which will allow compact and low-cost THz imaging, thus maximizing its potential for translation into clinical practice. The proposal explains our plans for accomplishing this ultimate goal. Specifically, we aim to further develop an existing apparatus that performs line- scanning of excised breast specimens, creating a 2D surface map of lesion margins. Development will consist of modeling THz-tissue interactions, creating tissue-simulated phantoms for normal (fatty/adipose, fibrous/glandular) and malignant tissue, imaging phantoms and finally breast specimens. Terahertz images of excised thin samples of breast tissue will be compared with histological images and the results analyzed with several different techniques. We will also obtain THz spectra of similar specimens and analyze these for signatures of known over-expressed proteins and other potential biomarkers for cancer. Finally, we will describe how we plan to translate this THz imaging technique into clinical use in the future. PUBLIC HEALTH RELEVANCE: We propose investigating a technology that will enable surgeons to detect cancerous tissue margins in real-time and in intraoperational settings;eliminating in many cases the need for repeat surgery due to post-surgical histopathological determination of remaining malignant tissue (i.e., "positive margins"). Repeat surgeries come at significant fiscal, temporal, and emotional cost for both patients and medical providers and reducing the need for them represents a clear and immediate benefit to humanity.